title: Tissue kallikrein protects cortical neurons against hypoxia/reoxygenation injury via the ERK1/2 pathway.
abstract: Systemic or local delivery of human tissue kallikrein gene (hTK) has been shown to be an effective strategy to alleviate cerebral ischemia/reperfusion (I/R) injury, and tissue kallikrein (TK) administration can suppress glutamate- or acidosis-mediated neurotoxicity in vitro. In the present study, the role of TK in hypoxia/reoxygenation (H/R) induced neuronal cell death was investigated. We found that TK administration could remarkably alleviate H/R-induced neuronal injury by reduction of LDH release and promotion of neuron viability. The protective effects of TK could be counteracted by bradykinin B2 receptor (B2R) antagonist HOE140, which could suppress up-regulation of TK on the ERK signal pathway under H/R condition. These results indicate that TK plays an important role in preventing neurons from H/R damage at least partially through the TK-B2R-ERK1/2 pathway.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Chen
authors.forename: Houguang
authors.initials: H
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Renliang
authors.initials: R
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology*; D019610:Cytoprotection; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology*; D020840:Tissue Kallikreins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
chemical_list: D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020840:Tissue Kallikreins; D001920:Bradykinin